ArticleEMBO molecular medicine2022
Inhibition of NPC1L1 disrupts adaptive responses of drug-tolerant persister cells to chemotherapy.
Article in EMBO molecular medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.
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Who cites it
58 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.
- Multilevel Mechanisms of Cancer Drug Resistance.International journal of molecular sciences · 2024Pooled it
- A four‑gene signature identifies TKI‑induced persister cells and uncovers a ZLN005‑induced pyroptotic vulnerability via the GSDME pathway in EGFR‑mutant lung cancer.Molecular medicine reports · 2026Article
- CRISPR screening reveals NPC1L1 as a key driver of glioblastoma progression via cholesterol metabolic regulation.MedScience · 2026Article
- The allosteric IDH1 inhibitor ivosidenib overcomes chemoresistance in intrahepatic cholangiocarcinoma models expressing wild-type IDH1.The Journal of clinical investigation · 2026Article
- Transfer of Damaged Mitochondria from Cancer Cells to Cancer-Associated Fibroblasts Promotes Tyrosine Kinase Inhibitor Tolerance in EGFR-Mutant Lung Cancer.Cancer research · 2026Article
- Drug-tolerant persister cells in lymphoid malignancies: from mechanisms to therapeutic opportunities.Frontiers in oncology · 2026Review
- SOS1 inhibition suppresses the emergence of osimertinib resistance to generate a durable response inScience signaling · 2025Article
- MAPK and mTORC1 signaling converge to drive cyclin D1 protein production to enable cell cycle reentry in melanoma persister cells.Science signaling · 2025Article
- NRF2-mediated persistent adaptation of oesophageal adenocarcinoma cells to HER2 inhibition.Oncogene · 2025Article
- EGFR-TKIs Induced DPP4 Drives Metabolic Reprogramming of Persister Cells in Lung Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Targeting cholesterol metabolism: a promising therapy strategy for cancer.Acta pharmacologica Sinica · 2025Review
- Cytoskeleton disruption and plasma membrane damage determine methuosis of normal and malignant cells.Cell & bioscience · 2025Article
- Drug-induced tolerant persisters in tumor: mechanism, vulnerability and perspective implication for clinical treatment.Molecular cancer · 2025Review
- Cytoplasmic Vacuolization: A Fascinating Morphological Alteration From Cellular Stress to Cell Death.Cancer science · 2025Review
- Targeting PKC as a Therapeutic Strategy to Overcome Chemoresistance in TNBC by Restoring Aurora Kinase B Expression.Journal of cellular and molecular medicine · 2025Article
- Combined blockade of GPX4 and activated EGFR/HER3 bypass pathways inhibits the development of ALK-inhibitor-induced tolerant persister cells in ALK-fusion-positive lung cancer.Molecular oncology · 2025Article
- Drug-tolerant persister cells in acute myeloid leukemia: pressing challenge and promising new strategies for treatment.Frontiers in medicine · 2025Review
- Nutraceutical Evaluation of Trigonelline's Therapeutic Potential by Targeting Bladder Cancer Stem Cells and Cancer-Associated Fibroblasts via Downregulation of TGFβ3/GLI2/YAP1 Signaling Hub.International journal of medical sciences · 2025Article
- Diagnosis and prognosis prediction of gastric cancer by high-performance serum lipidome fingerprints.EMBO molecular medicine · 2024Article
- Combining Photodynamic Therapy and Targeted Drug Delivery Systems: Enhancing Mitochondrial Toxicity for Improved Cancer Outcomes.International journal of molecular sciences · 2024Review
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Entering a drug-tolerant persister (DTP) state of cancer cells is a transient self-adaptive mechanism by which a residual cell subpopulation accelerates tumor progression. Here, we identified the acquisition of a DTP phenotype in multidrug-resistant (MDR) cancer cells as a tolerance response to routine combination treatment. Characterization of MDR cancer cells with a DTP state by RNA-seq revealed that these cells partially prevented chemotherapy-triggered oxidative stress by promoting NPC1L1-regulated uptake of vitamin E. Treatment with the NPC1L1 inhibitor ezetimibe further enhanced the therapeutic effect of combinatorial therapy by inducing methuosis. Mechanistically, we demonstrated that NRF2 was involved in transcriptional regulation of NPC1L1 by binding to the -205 to -215 bp site on its promoter. Decreased DNA methylation was also related partially to this process. Furthermore, we confirmed that a triple-combination of chemotherapeutic agents, verapamil, and ezetimibe, had a significant anti-tumor effect and prevented tumor recurrence in mice. Together, our study provides a novel insight into the role of DTP state and emphasizes the importance of disrupting redox homeostasis during cancer therapy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.